Diabetes Drug Alert: Canagliflozin (Invokana) 

Pearls of Practise

By Dr Vinod Gujral

For the prescription of Canagliflozin, it is important that Health care professionals should follow the recommendations in the canagliflozin drug labels. Monitor patients for the signs and symptoms described above and advise patients to seek medical advice if they experience them. following Drug Alerts should be kept in mind.

• In 2016, FDA issued a drug alert on canagliflozin, linking it to increased risk of leg and foot amputations based on interim results of clinical trial. The FDA has not determined whether canagliflozin increases the risk of leg and foot amputations.The medical community and the public will be updated once the FDA has more information.There are two trials that are on-going looking at this issue.


• In 2015, the FDA had added a new warning and precaution in Invokana; it may increase risk of bone fractures and decrease bone mineral density in T2DM patients.Clinical trials showed Canagliflozin caused loss of bone mineral density at the hip and lower spine.Patients who want to start Invokana or had high risk of bone fracture should talk to their health care professionals before taking Invokana.The FDA will update label to include new data on the low annual incidence of bone fracture and risk of decreased bone mineral density.


• In March 2016, a study published in Diabetes Care by Anne L. Peters, Robert R. Henry, Payal Thakkar, Cindy Tong, Maria Alba concluded that Canagliflozin was associated with an increased incidence of serious AEs of DKA in patients with type 1 diabetes inadequately controlled with insulin. Mitigation strategies are needed for use in future clinical trials to reduce the risk of DKA with canagliflozin treatment in patients with type 1 diabetes.

Canagliflozin and risk of Leg and Foot Amputations

Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA is going to investigate further

Canagliflozin is a prescription medicine used with diet and exercise to lower blood sugar in adults with type 2 diabetes. It belongs to a class of drugs called sodium-glucose cotransporter-2 (SGLT2) inhibitors. Canagliflozin lowers blood sugar by causing the kidneys to remove sugar from the body through the urine. It is available as a single-ingredient product under the brand name Invokana and also in combination with the diabetes medicine metformin under the brand name Invokamet

However, a month back, The U.S. Food and Drug Administration (FDA) issued an alert on the drug informing the public about interim safety results from an ongoing clinical trial that found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin (Invokana, Invokamet). "We have not determined whether canagliflozin increases the risk of leg and foot amputations. We are currently investigating this new safety issue and will update the public when we have more information," the alert added.

This came after, the ongoing Canagliflozin Cardiovascular Assessment Study (CANVAS) clinical trial, where the trial's independent data monitoring committee (IDMC) identified an increased risk of leg and foot amputations. The amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo, which is an inactive treatment. An interim analysis showed that over a year's time, the risks of amputation for patients in the trial were equivalent to:

• 7 out of every 1,000 patients treated with 100 mg daily of canagliflozin


• 5 out of every 1,000 patients treated with 300 mg daily of canagliflozin


• 3 out of every 1,000 patients treated with placebo

Patients in the CANVAS trial have been followed for an average of 4.5 years to date. The IDMC has recommended, based on an overall assessment, that the CANVAS trial continue.

The IDMC has also reported that a second, similar trial evaluating canagliflozin, the CANVAS-R trial, has not shown the same risks of increased leg and foot amputations to date. Patients in the CANVAS-R trial have been followed for an average of 9 months.

Canagliflozin and Bone Fractures

This is not the first time FDA issued a warning related to Canagliflozin ( Invokana) (September 15th, 2015 )

In September 2015, the FDA had added a new warning and precaution in Invokana; it may increase risk of bone fractures and decrease bone mineral density in T2DM patients.

This was based on Clinical trials that showed Canagliflozin caused loss of bone mineral density at the hip and lower spine.Patients who want to start Invokana or had high risk of bone fracture should talk to their health care professionals before taking Invokana.2.

Diabetic Ketoacidosis With Canagliflozin

The Study concluded that Canagliflozin was associated with an increased incidence of serious AEs of DKA in patients with type 1 diabetes inadequately controlled with insulin. Mitigation strategies are needed for use in future clinical trials to reduce the risk of DKA with canagliflozin treatment in patients with type 1 diabetes.

Sources:-

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm501565.htm

http://dx.doi.org/10.2337/dc15-1995

http://www.fda.gov/Drugs/DrugSafety/ucm461449.htm